. This proposal will address the hypothesis that the distribution of isolates of C. neoformans among patients with AIDS is not random. Strains to be compared will be isolated globally from patients with AIDS, as well as patients without AIDS and sources in the environment. The project will evaluate DNA fingerprinting methods and analyze the distribution and relatedness of strains of C. neoformans, investigate the population genetics of C. neoformans by developing codominant genotypic markers, and identify genetic markers that signify clinically relevant properties, such as drug resistance or tissue tropisms. This research will explore the mechanisms whereby genetic traits may be exchanged among strains and the evolution of pathobiological phenotypes. The investigator believes that the results of this investigation will pertain to the biology of C. neoformans and provide useful tools to study the epidemiology, diagnosis and prevention of cryptococcosis. Practical methods will be developed to identify problematic strains in the clinical laboratory, which will facilitate the management of the disease in AIDS patients.